1. Field of the Invention
The present invention relates generally to the fields of chemotherapeutic treatments. More particularly, it concerns the use of ibuprofen, a non-steroid anti-inflammatory drug, in the treatments of malignancies such as cancer. In other embodiments, the present invention relates to the therapeutic uses of ibuprofen in the treatments of Alzheimer's and Alzheimer's-related diseases.
2. Description of Related Art
Neoplastic diseases are conditions in which the abnormal proliferation of cells results in a cancerous mass of cells. These cancers are responsible for hundreds of thousands of deaths in the U.S. alone each year. Unfortunately, neoplasia possess a wide variety of abnormalities in structure and function that render them difficult to attack. Thus, new and effective treatments of neoplastic diseases are valuable for the prevention and/or cure of cancer.
Alzheimer's Disease is a complex pathology that affects 5 to 11% of the population over 65 years, and as much as 47% of the population over the age of 85 in developed countries. The health care cost per patient for this disease are staggering, given the severe physical and mental debilitation of the patients. If preventive measures are not found, the numbers can be expected to increase dramatically as the aging population increases (Flier and Underhill, 1991), further escalating costs.
A class of compounds with a potential therapeutic value in both of the aforementioned afflictions is non-steroidal anti-inflammatory drugs (NSAID). NSAIDs are commonly used as anti-inflammatory agents and as analgesics. Physiologically, these compounds are known to inhibit the biosynthesis of prostaglandins by inhibition of the cyclooxygenase enzyme (Buckley et al., 1990).
Ibuprofen is an NSAID that acts by inhibiting cyclooxygenase and omithine decarboxylase activities. However, it appears that this effect also is associated with a number of undesirable effects, including toxicity, because the inhibition of prostaglandin synthesis leads to gastrointestinal distress, possible renal and hepatic toxicities, and other malfunctions including thrombocytopenia and leukopenia (leading to subsequent agranulocytosis). Agranulocytosis is a life threatening condition that develops rapidly and is difficult to detect, and has been described for several NSAIDs including indomethacin, ketoprofen and ibuprofen. Thus, NSAIDs are contraindicated in patients whose immune systems are compromised by HIV infection, chemotherapy, ionizing irradiation, corticosteroids, immunosuppressives and the like and also in conditions such as emphysema, bronchiectasis, diabetes mellitus, leukemia and the like (Broda et al., 1992).
Ibuprofen, like many other NSAIDs, exhibits molecular chirality, and thus can be found in R- and S-enantiomeric forms. Such compounds typically are produced in enantiomeric mixtures which subsequently can be separated into the individual enantiomers (Yamaguchi et al., 1987). It is generally alleged that the S-enantiomer has the higher prostaglandin synthesis activity of the two enantiomers (Yamaguchi et al., 1987). Indeed Caldwell et al. (1988) have suggested that the R-isomer functions, at best, as prodrugs for the therapeutically active S-forms when the racemic drug is administered. Further, Caldwell et al. suggest that at worst the R-enantiomers of NSAIDs are undesirable impurities in an active drug causing difficulties due to non-stereoselective toxicity.
NSAIDs previously have been shown to be therapeutically effective against a variety of cancers (Heath et al., 1994). However, the toxicity and side effects of S-enantiomers, as described above, make NSAIDs unfavorable for use in human treatment. Indeed, many NSAIDs have been removed from common usage even as analgesics. It would be a fruitful endeavor to identify formulations of NSAIDs for use as treatments of cancers and other diseases, but without the aforementioned disadvantages of the S-enantiomeric compositions.